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Discovery of the streptoketides by direct cloning and rapid heterologous expression of a cryptic PKS II gene cluster from streptomyces sp. Tü 6314.
J. Org. Chem. 85, 664-673 (2020)
Genome sequencing and bioinformatic analysis have identified numerous cryptic gene clusters that have the potential to produce novel natural products. Within this work, we identified a cryptic type II PKS gene cluster (skt) from Streptomyces sp. Tu 6314. Facilitated by linear plus linear homologous recombination-mediated recombineering (LLHR), we directly cloned the skt gene cluster using the Streptomyces site-specific integration vector pSET152. Direct cloning allowed for rapid heterologous expression in Streptomyces coelicolor, leading to the identification and structural characterization of six polyketides (three known compounds and new streptoketides), four of which exhibit anti-HIV activities. Our study shows that the pSET152 vector can be directly used for LLHR, expanding the Rec/ET direct cloning toolbox and providing the possibility for rapid heterologous expression of gene clusters from Streptomyces.
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4.335
0.952
8
13
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Microbial Natural-products; Starter Unit; Polyketide Synthase; Biosynthesis; Daunorubicin; Dna; Anthracycline; Ketosynthase; Doxorubicin; Coelicolor
Language
english
Publication Year
2020
Prepublished in Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
0022-3263
e-ISSN
1520-6904
Quellenangaben
Volume: 85,
Issue: 2,
Pages: 664-673
Publisher
American Chemical Society (ACS)
Publishing Place
1155 16th St, Nw, Washington, Dc 20036 Usa
Reviewing status
Peer reviewed
Institute(s)
Institute of Virology (VIRO)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-502700-001
WOS ID
WOS:000508468900034
Scopus ID
85077473986
PubMed ID
31746205
Erfassungsdatum
2019-12-20